Memory enhancement by the administration of Δ5-androstene-3β-ol-7,17-dione and 3β esters thereof

ABSTRACT

The memory of a healthy mammal and the memory of a mammal with age impaired memory can be improved by administering an effective amount of Δ5-Androstene-3β-ol-7,17-dione and 3β esters thereof.

FIELD OF THE INVENTION

The invention relates to the use of pharmaceuticals and dietarysupplements to improve memory.

BACKGROUND

Mankind has sought ways to improve memory for years, including effortsranging from the consumption of specific foods to meditation. Whilecertain of these techniques have demonstrated limited success inimproving memory, the search continues for alternative means forimproving memory.

SUMMARY OF THE INVENTION

We have discovered that the memory of both a healthy mammal and a mammalwith age impaired memory can be improved by administering an effectiveamount of Δ5-Androstene-3β-ol-7,17-dione and 3β esters thereof.

DETAILED DESCRIPTION OF THE INVENTION INCLUDING A BEST MODE

Definitions

As utilized herein, the term "healthy mammal" means a mammal having nodiagnosed disease, disorder, infirmity, or ailment known to impair orotherwise diminish memory.

The Steroid

The steroid Δ5-androstene-3β-ol-7,17 dione is a derivative ofdehydroepiandrosterone (DHEA) which does not appreciably stimulate,increase or otherwise enhance the production of sex hormones. Thesteroid is commercially available from a number of sources includingSteraloids, Inc. of Newton, R.I. The 3β acetyl form of the steroid iscommercially available from Humanetics Corporation of St. Louis Park,Minn. A number of procedures are available for synthesizingΔ5-androstene-3β-ol-7,17-dione and the 3β acetyl form from DHEA, withone such procedure described in U.S. Pat. No. 5,296,481.

Precursors of Δ5-androstene-3β-ol-7,17 dione may also be usefullyemployed for improving memory. Such precursors are readily metabolizedin vivo to the active Δ5-androstene-3β-ol-7,17 dione. One example ofsuch a metabolizable precursor is the commercially availableΔ5-androstene3β-acetyl-7,17 dione. The 3β-acetyl group is hydrolyzed invivo by esterases located in the blood and various tissues to producethe active Δ5-androstene-3β-ol-7,17 dione, and is believed to be lesssusceptible to oxidation during the manufacturing process than thehydroxy group found on the active Δ5-androstene-3β-ol-7,17 dione. Othermetabolizable precursors include Δ5-androstene-3β, 17β-diol-7-one,Δ5-androstene-3β, 7α-diol-17-one, Δ5-androstene-3β, 7β-diol-17-one andthe corresponding esters of these steroids.

Administration

Administration Route

The steroid can be administered by virtually any of the commonlyaccepted practices for the administration of pharmaceutical preparationsincluding specifically, but not exclusively, mucosal administration,oral consumption, ocular administration, subcutaneous injection,transdermal administration, etc.

Mucosal administration of the steroid includes such routes as buccal,endotracheal, nasal, pharyngeal, rectal, sublingual, vaginal, etc. Foradministration through the buccal/sublingual/pharyngeal/endotrachealmucosa, the steroid may be formulated as an emulsion, gum, lozenge,spray, tablet or an inclusion complex such as cyclodextrin inclusioncomplexes. Nasal administration is conveniently conducted through theuse of a sniffing power or nasal spray. For rectal and vaginaladministration the steroid may be formulated as a cream, douch, enema orsuppository.

Oral consumption of the steroid may be effected by incorporating thesteroid into a food or drink, or formulating the steroid into a chewableor swallowable tablet.

Ocular administration may be effected by incorporating the steroid intoa solution or suspension adapted for ocular application such as drops orsprays.

Subcutaneous administration involves incorporating the steroid into apharmaceutically acceptable and injectable carrier.

For transdermal administration, the steroid may be convenientlyincorporated into a lipophilic carrier and formulated as a topical cremeor adhesive patch.

Dose Rate

The range of dosages and dose rates effective for achieving the desiredbiological properties and characteristics may be determined inaccordance with standard industry practices. These ranges can beexpected to differ depending upon whether the desired response is theprophylactic, modulatory, ameliorative or curative in nature.

EXPERIMENTAL

Experiment 1

(Aged Mice)

Aged, two year old mice were tested in the Morris water maze procedureby training the mice to locate the pedestal in less than 15 seconds inthree consecutive trials. Immediately upon completion of training onegroup of mice was treated with DHEA (20 mg/kg) and a second grouptreated with an eqimolar amount of Δ5-Androstene-3β-acetyl-7,17-dione.Two weeks after treatment the time to rescue was timed in the Morriswater maze procedure at: Control 36 seconds, DHEA 27 seconds, andΔ5-Androstene-3β-acetyl-7,17-dione 13 seconds.

Experiment 2

(Scopolamine-Induced Amnesia)

Groups of 13 to 16 C57BL76 mice (35 gm) were tested in the Morris watermaze procedure by training the mice to locate the pedestal in less than15 seconds in three consecutive trials. Immediately upon completion oftraining the mice in each of three groups were treated with scopolamine(1 mg/kg), scopolamine+DHEA, orscopolamine+Δ5-Androstene3β-acetyl-7,17-dione. Six days after treatmentthe average time (sec) to rescue was timed in the Morris water mazeprocedure at: Control 12.2±1.8; scopolamine 20.0±3.6; scopolamine+DHEA9.7±1.6; and scopolamine+Δ5-Androstene-3β-acetyl-7,17-dione 8.3±1.8,wherein control vs. scopolamine p</=0.055; scopolamine vs.scopolamine+DHEA p</=0.02; and scopolamine vs.scopolamine+Δ5-Androstene-3β-acetyl-7,17-dione p</=0.008.

We claim:
 1. A method for treating a mammal in need of improved memory,wherein said mammal has no diagnosed disease, disorder, infirmity orailment known to impair or otherwise diminish memory, comprising thestep of administering to the mammal an effective memory-improving amountof a steroid selected from the group consisting ofΔ5-Androstene-3β-ol-7,17-dione and 3β esters thereof.
 2. The method ofclaim 1 wherein the step of administering the steroid to a mammalcomprises the step of administering the steroid to a human.
 3. Themethod of claim 2 wherein the method improves the long term memory ofthe human.
 4. The method of claim 2 wherein the step of administeringthe steroid comprises the step of injecting the steroid.
 5. The methodof claim 2 wherein the step of administering the steroid comprises thestep of inducing ingestion of the steroid.
 6. The method of claim 2wherein the step of administering the steroid comprises the step ofadministering Δ5-Androstene-3β-acetyl-7,17-dione.